Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional “cocktail administration” is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug conjugates through coupling the conventional chemotherapeutics to a carrier (such as antibody and peptide) provide an alternative strategy to improve therapeutic efficacy and simultaneously reduce the unspecific toxicities, by virtue of the advantages of highly specific targeting ability and potent killing effect. Although 14 antibody–drug conjugates (ADCs) have been approved worldwide and more are being investigated in clinical trials so far, several limitations have been disclosed during clinical application. Compared with ADCs, peptide-drug conjugates (PDCs) possess several advantages, including easy industrial synthesis, low cost, high tissue penetration and fast clearance. So far, only a handful of PDCs have been approved, highlighting tremendous development potential. Herein, we discuss the progress and pitfalls in the development of ADCs and underline what can learn from ADCs for the better construction of PDCs in the future.

Healthy sleep is vital to maintaining the body's homeostasis. With the development of modern society, sleep disorder has gradually become one of the most epidemic health problems worldwide. Shumian capsule (SMC), a kind of traditional Chinese medicine (TCM) commonly used for insomnia, exhibits antidepressant and sedative effects in clinical practice. However, the underlying mechanisms have not been fully clarified. With the aid of a network pharmacology approach and function enrichment analysis, we identified the involvement of melatonin receptors in the antidepressant and sedative effects of SMC. In sleep-deprived mice, SMC treatment significantly alleviated insomnia and relevant mental alterations by improving both sleep latency and sleep duration. However, ramelteon, a selective melatonin receptor agonist that has been approved for the treatment of insomnia, only improved sleep latency. Additionally, SMC exhibited comparable effects on mental alterations with ramelteon as determined by an open-field test (OFT) and forced swimming test (FST). Mechanistically, we revealed that the melatonin receptor MT1 and MT2 signaling pathways involved the therapeutic effects of SMC. In addition to the single effect of traditional melatonin receptor agonists on treating sleep onset insomnia, SMC had therapeutic potential for various sleep disorders, such as sleep onset insomnia and sleep maintenance insomnia. Convergingly, our findings provide theoretical support for the clinical application of SMC.

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